The immune system: basis of so much health and disease: 5. complement Crispian Scully Eleni A Georgakopoulou Yazan Hassona Dental Update 2024 44:7, 707-709.
The immune system is the body's primary defence mechanism against infections, and disturbances in the system can cause disease if the system fails in defence functions (in immunocompromised people), or if the activity is detrimental to the host (as in auto-immune and auto-inflammatory states). A healthy immune system is also essential to normal health of dental and oral tissues. This series presents the basics for the understanding of the immune system, this article covers complement and other mediators of inflammation.
Clinical Relevance: Modern dental clinicians need a basic understanding of the immune system as it underlies health and disease.
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’Complement’ is a system of at least nine plasma proteins, synthesized mainly by the liver. Complement functions include:
Complement proteins can be activated in sequence (comparable to the blood clotting cascade) by a variety of triggering agents.
There are at least three complement pathways:
This is activated by immunoglobulins (antibodies), either attached to a cell surface antigen or as immune (antigen-antibody) complexes. Binding of complement component C1q (Figure 1) to IgG or IgM antibodies activates the rest of the complement pathway by auto-catalytically converting another component of C1, to an active enzyme that ultimately converts C3 to C3a, C3b and thus to C5a and C5b. C1 can also be activated by C-reactive protein, and serum amyloid protein (Figure 2).
This is activated by a range of foreign cell-surface constituents such as of Gram-positive and Gram-negative bacteria (eg bacterial endotoxin [lipopolysaccharides, LPS], polysaccharide capsules, fungi, some viruses, tumour cells and aggregates of IgE and properdin. Activation of the alternative pathway requires four proteins, C3, Factor B, Factor D and properdin (Figure 2).
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